Separation of Selected Imidazole Enantiomers Using Dual Cyclodextrin System in Micellar Electrokinetic Chromatography

Abstract

Cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) method was developed for simultaneous enantioseparation of three imidazole drugs namely tioconazole, isoconazole and fenticonazole. Three easily available and inexpensive cyclodextrins namely 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), 2-hydroxypropyl-γ-cyclodextrin (HP-γ-CD) and heptakis(2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD) were evaluated to discriminate the six stereoisomers of the drugs. However, none of the three CDs gave a complete enantioseparation of the drugs. Effective enantioseparation of tioconazole, isoconazole and fenticonazole was achieved using a combination of 35 mM HP-γ-CD and 10 mM DM-β-CD as chiral selectors. The best separation using both HP-γ-CD and DM-β-CD (35 mM:10 mM) as chiral selectors were accomplished in background electrolyte (BGE) containing 35 mM phosphate buffer (pH 7.0), 50 mM sodium dodecyl sulfate (SDS) and 15% (v/v) acetonitrile at 27 kV and 30 °C with all peaks resolved in less than 15 min with resolutions, Rs 1.90-27.22 and peak efficiencies, N > 180 000. The developed method was linear over the concentration range of 25-200 mg l(-1) (r(2) > 0.998) and the detection limits (S/N = 3) of the three imidazole drugs were found to be 2.7-7.7 mg l(-1). The CD-MEKC method was successfully applied to the determination of the three imidazole drugs in spiked human urine sample and commercial cream formulation of tioconazole and isoconazole with good recovery (93.6-106.2%) and good RSDs ranging from 2.30-6.8%.

New Conditions for the Effective Synthesis of Tri and Tetrasubstituted Imidazoles Catalysed by Recyclable Indium (III) Triflate and Magnesium Sulfate Heptahydrate

“…All products obtained (Table 5) were characterised by IR, 1 H, 13 C NMR, MS analyses for novel products (Figs S1-S48, ESI), and known products were compared with their published physical properties. After determination of the suitable reaction conditions, the scope of this MCR was examined using various starting materials under standard conditions.…”

Enantioseparation of nine indanone and tetralone derivatives by HPLC using carboxymethyl‐β‐cyclodextrin as the mobile phase additive

“…5 Furthermore, a chiral HPLC column cannot be universally used due to its strict stereospecificity. 9 The widely used CD in chiral separation is due to the hydrophobic cavity, which can form an inclusion complex with a large number of analytes containing an aromatic moiety or a long hydrocarbon chain. 7,8 Cyclodextrin (CD) and their derivatives are commonly used as mobile phase additives in HPLC as well as capillary electrophoresis (CE).…”

“…7,8 Cyclodextrin (CD) and their derivatives are commonly used as mobile phase additives in HPLC as well as capillary electrophoresis (CE). 9 The widely used CD in chiral separation is due to the hydrophobic cavity, which can form an inclusion complex with a large number of analytes containing an aromatic moiety or a long hydrocarbon chain. [10][11][12] Many researchers have carried out a variety of experiments to study enantioseparation and inclusion complex using β-CD as mobile phase additive recently.…”

Theoretical and Molecular Docking Study of Ketoconazole on Heptakis(2,3,6‐tri‐O‐methyl)‐β‐cyclodextrin as Chiral Selector

“…Among them, CDs are the most widely used due to their excellent chiral recognition abilities. CDs and their derivatives have been extensively used as chiral selectors in the study of enantioseparation of chiral compounds . To understand the chiral recognition mechanism underlying the chiral separation using CDs and their derivatives as chiral selectors, great advances have been made using experimental and theoretical methods during the past decade.…”

“…CDs and their derivatives have been extensively used as chiral selectors in the study of enantioseparation of chiral compounds . To understand the chiral recognition mechanism underlying the chiral separation using CDs and their derivatives as chiral selectors, great advances have been made using experimental and theoretical methods during the past decade. Numerous theoretical studies such as molecular modeling have been performed in order to explain experimental findings and to elucidate the enantioseparation mechanism of enantiomers with chiral selectors.…”